Poster Presentation ESA-SRB-ANZBMS 2024 in conjunction with ENSA

The ups and downs of Cushing’s Disease  (#583)

Mauli Govinna 1 2 , Ann McCormack 1 2 3
  1. Department of Endocrinology and Diabetes, St Vincent's Hospital , Darlinghurst , NSW, Australia
  2. Garvan Institute of Medical Research , Darlinghurst, New South Wales, Australia
  3. School of Clinical Medicine, University of New South Wales, New South Wales, Australia

Case:
Mrs JD is a 43 year old initially diagnosed with Cushing’s Disease (CD) in 2001, who underwent Transphenoidal Surgery (TSS) in 2002. She re-presented with symptoms of weight gain and irregular menses in 2016 without biochemical hypercortisolism. MRI revealed a small hypointensity in the right posterior gland.

She delivered a healthy baby in December 2021 via donor egg In Vitro Fertilisation (IVF). Post-partum she suffered three insufficiency fractures. Repeat biochemistry confirmed hypercortisolism. MRI studies in 2022 did not display a definitive lesion. She achieved normalisation of LNSC and 24hr UFC with low dose ketoconazole, ceased due to intolerance.

A second TSS was performed in July 2023 in context of biochemical and clinical recurrence of hypercortisolism and a well-defined right sided 2.5 mm pituitary microadenoma on MRI. Histopathology revealed a small lactrotroph adenoma (Pit1 and prolactin positive; T-pit and ACTH negative) with surrounding normal pituitary tissue and no convincing Crooke cell changes. Review of original tissue from TSS in 2002 confirmed a corticotroph adenoma positive for ACTH , T-pit and negative for other transcription factors. The Ki67 index was <1%.

Ongoing testing shows a pattern of biochemical ‘cycling’. Imaging reveals no recurrent adenoma (February 2024) and no avid lesions on Ga 68 Dotatate PET/CT. Given desire for pregnancy, she commenced on cabergoline in June 2024 with consideration of bilateral adrenalectomy in future.

Discussion:
This case of Cyclical Cushing’s Syndrome (cCS), in which biochemical hypercortisolism alternates with phases of physiological cortisol concentrations1, highlights challenges in diagnosis and management due to long troughs or rapid cycling. Bilateral adrenalectomy offers immediate control of cortisol excess in patients not responsive to medical therapy2. Shorter duration of Cushing’s disease, presence of an adenoma on imaging and a high plasma ACTH concentration post- adrenalectomy are significant predictive factors for corticotroph tumor progression (Nelson’s syndrom

 

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  1. Nowak E, Vogel F, Albani A, Braun L, Rubinstein G, Zopp S, Ritzel K, Beuschlein F, Theodoropoulou M, Reincke M. Diagnostic challenges in cyclic Cushing's syndrome: a systematic review. Lancet Diabetes Endocrinol. 2023 Aug;11(8):593-606. doi: 10.1016/S2213-8587(23)00150-X. Epub 2023 Jul 7.PMID: 37429301.
  2. Lynnette K. Nieman, Beverly M. K. Biller, James W. Findling, M. Hassan Murad, John Newell-Price, Martin O. Savage, Antoine Tabarin, Treatment of Cushing's Syndrome: An Endocrine Society Clinical Practice Guideline, The Journal of Clinical Endocrinology & Metabolism, Volume 100, Issue 8, 1 August 2015, Pages 2807–2831, https://doi.org/10.1210/jc.2015-1818
  3. Guillaume Assié, Hélène Bahurel, Joël Coste, Stéphane Silvera, Michèle Kujas, Marie-Annick Dugué, Foued Karray, Bertrand Dousset, Jérôme Bertherat, Paul Legmann, Xavier Bertagna, Corticotroph Tumor Progression after Adrenalectomy in Cushing’s Disease: A Reappraisal of Nelson’s Syndrome, The Journal of Clinical Endocrinology & Metabolism, Volume 92, Issue 1, January 2007, Pages 172–179, https://doi.org/10.1210/jc.2006-1328